Copolymer-1 is a complex mixture of polypeptides prepared from the polymerization of the amino acids glutamic acid, lysine, alanine and tyrosine. Copolymer-1 also is known as glatiramer acetate (CAS No. 147245-92-9) and has the following structural formula:(Glu,Ala,Lys,Tyr)xXCH3COOH(C5H9NO4.C3H7NO2.C6H14N2O2.C9H11NO3)x.XC2H4O2 See Physician's Desk Reference, Thomson P D R, Montvale, N.J., p. 3297 (2007).
Glatiramer acetate (GA) is the active ingredient of COPAXONE® (Teva Pharmaceutical Industries Ltd., Israel), which comprises the acetate salts of synthetic polypeptides containing four naturally occurring amino acids: L-glutamic acid, L-alanine, L-tyrosine, and L-lysine, with a reported average molar fraction of 0.141, 0.427, 0.095, and 0.338, respectively. Id. Glatiramer acetate has been widely used in the treatment of multiple sclerosis and has been clinically shown to reduce the average relapse rate in people with the relapsing-remitting form of multiple sclerosis (RRMS).
Analytical tests that can be used to characterize glatiramer acetate are of benefit toward defining the structure of this complex peptide mixture and similar complex peptide mixtures. Such analytical methods also are useful for analyzing the properties or quality of a particular batch of the mixture, for analyzing intermediate stages in the preparation of glatiramer acetate, or for identifying and isolating bioreactive components of a complex mixture or signature components of the process for making the same. Thus, there is a need in the art for analytical tests that can be used to characterize glatiramer acetate and similar complex peptide mixtures. The presently disclosed subject matter addresses, in whole or in part, these and other needs in the art.